Starch-based soft chewables are generally known in the art. Starch-based extrudates containing drug substances, specific aromas, and bodying agents are described in European Patent No. 1298655 B1 (Kalbe et al.) Kalbe et al. also describe processes for preparing the starch-based extrudates at a temperature less than 150° C. The examples of this patent describe soft chewables containing either 55% wheat flour or 45% maize starch as the primary matrix component. The extrusion temperature mentioned in the examples is 120° C. which is very high for practical purposes especially when the active ingredient is thermolabile.
Ductile soft chewables containing partially pre-gelatinized starch as the primary matrix material are reported in U.S. Patent Application Publication No. 2008/0222684 (Isele). Isele mentions that partially pre-gelatinized starch is needed for obtaining the desired ductility of the final product. Accordingly, examples 1-3 of Isele describe chewables containing 41%, 31.9%, and 36.7% pre-gelatinized starch, respectively. The chewables are prepared by an extrusion process that requires the equipment to be pre-cooled below room temperature (i.e., <10° C.). The mixture to be extruded is also cooled continuously during the extrusion process with the help of external coolers so that the product temperature does not exceed 40° C. The chewables are filled into boxes and cured for about 24 hours at ambient temperature and a relative humidity of less than 60%. Each formulation contains 1.5% sodium chloride to enhance payability and to bind moisture.
Soft chews for equines and canines are described in International Patent Publication WO 2004/014143 (Huron). The chewables essentially contain flavoring, starch, sugar, and an oil component. The moisture content is less than 15%. The equine soft chews mentioned in example 18 do not contain meat flavor. The disintegration time was reported as 14.45 min. However, the meat based canine chews reported in example 2 show a disintegration time of greater than 60 min. For both examples, melted polyethylene glycol (70° C.) was used to prepare a wet granulation mix.
Great Britain Patent No. 2300103B (Gilberston) describes palatable dog biscuits containing partially gelatinized starch and creatine prepared by an extrusion process at temperatures up to 130° C. This process is unsuitable for thermolabile drugs.
Conventional use of starch materials (e.g., corn starch, wheat starch, rice starch, pregelatinized starch and partially gelatinized starch) as binders, moisture retention aids and/or bodying agents to render the formulation soft and chewable can inhibit the desired disintegration of the soft chewable and dissolution profile of the active ingredient, in particular, the starch material swells when contacted with water and can prohibit rapid disintegration of the soft chewable product and subsequent dissolution of the active ingredient from the soft chew matrix in a reasonable amount of time. Other conventional ingredients used in soft chewable formulations may also have deleterious effects on the desired disintegration and dissolution profile of the product. For example, oils and waxes are often used as humectants to prevent drying and improve storage stability of the soft chewable. However, these hydrophobic ingredients can finely coat the active ingredient with a moisture-repelling barrier and thereby inhibit dissolution of the active ingredient upon administration.
Other materials used in conventional soft chewable formulations also have drawbacks. Soya products (e.g., hydrolyzed soy protein) are used as a moisture retention aid and/or filler or extender and also improve payability. However, soya products tend to exhibit a certain lack of uniformity and, as a result, when used as excipients contribute undesirably to interbatch variations and undermine quality control. Glycols (e.g., polyethylene glycol (PEG)) are another example of a humectant or moisture retention aid. Higher molecular weight glycols are typically added, to the formulation as a melt and the resulting soft chewable must be tempered for a sufficient period of time to allow the glycol to resolidify, which complicates and undesirably extends processing.
Therefore, while soft chewable formulations are known, there remains a need for an improved soft chewable for delivering drugs and other active ingredients to animals that is palatable, storage stable and disintegrates relatively quickly upon administration while avoiding some of the drawbacks associated with conventional soft chewable formulations and processing.
Further, there remains a need for processes for preparing improved soft chewables that may be practiced economically on a commercial scale at ambient or room temperatures and that are suitable for use with thermolabile drugs.